This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objective of this research is to define the mechanisms occurring within the primate corpus luteum (CL) that are critical for its development and regression. Evidence obtained from nonprimate species indicates that prostaglandins (PGs) regulate luteal structure-function, but their role in primate luteal physiology have not been defined. Preliminary data demonstrated that the expression of PGE2 synthesis (prostaglandin-endoperoxide synthase 2, PTGS2;microsomal PGE2 synthase-1, PTGES) and signaling (PGE2 receptor 3, PTGER3) components peak in the primate CL through the period of its development. Moreover, expression of the PGE2 synthesizing and signaling components significantly decreased preceding the period of functional regression of the CL, which also coincided with increasing levels of PGF2a receptor (PTGFR) expression. Thus, experiments will be performed to test the hypothesis that PGE2 actions are critical for primate luteal development, while PGF2a serves as a critical initiator of luteolysis. Studies are proposed that will assess the role PGE2 signaling plays in the development of the primate CL and evaluate whether PGF2a signaling is required for the demise of the CL at the end of the luteal phase. Protocols blocking intraluteal PG synthesis via a PTGS2 selective inhibitor will determine their role in CL development. The ablation of PG synthesis in the developing CL will be combined with the restoration of PTGER3 signaling through the use of a selective PTGER3 agonist. Progress to date includes the initial screening and vehicle treatment of animals in preparation for administration of a selective PTGS2 inhibitor and a PGF2a antagonist.